Monthly Archives: September 2007

Photodynamic therapy (PDT) is a nonsurgical, minimally invasive treatment that uses a light source to activate light-sensitive drugs or photosensitizers in the treatment of cancer and other diseases. PDT has been successfully employed to treat early carcinomas of the oral cavity and larynx preserving normal tissue and vital functions of speech and swallowing.

Two hundred seventy-six patients with early carcinomas of the oral cavity and larynx were treated from 1990 to 2006. Cure rates with a single treatment for early laryngeal and oral cancers were 91% and 94%, respectively. PDT is an effective primary and alternative treatment modality for early oral cavity and laryngeal cancers.

Drinking alcohol increases risk of head and neck cancer, but stopping use of alcoholic drinks reduces the risk, according to a new study published in the September 2007 issue of the International Journal of Cancer.

The study led by researchers at the Centre for Addition and mental Health (CAMH), Ontario, Canada, showed a relationship between alcohol consumption and an increased risk for cancer of the esophagus, larynx and oral cavity.

In the epidemiologic study, CAMH Principal Investigator Dr. Jürgen Rehm and colleagues analyzed literature from 1966 to 2006 and found that the risk of esophageal cancer almost doubled in the first two years following cessation of alcohol drinking.

The researchers explained that many people stopped drinking at a time they might have developed a condition, which might manifest two years after the cessation of alcohol drinking.

But the risk decreased rapidly and significantly later. They found after ten years of cessation, risk of head and neck cancer decreased significantly.

After 20 years, the risks for both cancers were similar to those for people who had never been drinking alcoholic beverages.

Dr. Rehm said “Alcohol cessation has very similar effects on risk for head and neck cancers as smoking cessation has on lung cancer. It takes about two decades before the risk is back to the risk of those who were never drinkers or never smokers.”

Drinking alcohol has been associated with a number of other cancers including breast, liver and colorectal cancers. But further studies are needed to clarify the inconsistency of previous studies, the researchers said.

Medical care is something we all need. Health care costs continue to rise and employment is no longer a guarantee that you’ll be covered. Millions of Americans work just to have health insurance – and still find themselves sick and broke.

Lisa Cristia is a cancer survivor. She was diagnosed with tongue and throat cancer four years ago. Her medical bills continue to pile up, even though she has health insurance. Lisa says, “I did have insurance. I thought it was enough and it would cover me and that the only battle that I would have to fight was the battle against cancer”. After going through $5,000 in savings and $14,000 in her 401-K, Lisa was still $65,000 in debt because of what her insurance didn’t cover.

Eventually, she was forced to file for bankruptcy. Lisa still needs follow up visits and medications, and that means more medical bills. She says, “It’s a lost future. I’m 38 years old, I am never gonna be able to buy a house. I’m never gonna be able to buy a brand new car, no matter how hard I work, no matter how much money I make. My credit is completely ruined”.

According to Ron Pollack, executive director of the consumer heath advocacy group Families USA — Lisa’s story is not unusual. He says health care cost is the #1 cause for people declaring bankruptcy in the United States today. In fact, nearly 47 million Americans or 16% of the population were without health insurance in 2005. That includes 27 million people who work full time. Pollack says, “the average cost family health coverage purchased through a group today is more than $12,000 a year. So even if you’re making, say $60,000 a year, that’s one fifth of your income just devoted to your premiums”. Lisa knows while she’s lucky – health insurance isn’t enough if you get seriously ill.

Despite improvements in surgical techniques and the development of novel chemoradiotherapy strategies, survival rates in patients with head and neck cancer has remained relatively unchanged over the last 30 years. While this could be due to the absence of any significant advancements in treatment techniques, newer targeted therapies now hold out great promise for the future. Pharmaceutical companies that succeed in increasing efficacy, lowering toxicity and improving survival rates can expect to gain position in the emerging European head and neck cancer therapeutics markets.

“Unlike traditional chemotherapy drugs, which not only attack tumours but harm healthy tissues as well, newer agents work by specifically targeting cancer cells,” notes Frost & Sullivan Programme Leader Paljit Mudhar. “A growing number of targeted therapies that predominantly attack cancer cells, leaving most healthy cells intact, are proving to be effective against a range of cancers including breast, colon, lung, kidney and head and neck cancers and lymphoma.”

Therefore, targeted therapies are expected to be a major growth driver for the head and neck cancer therapeutics market in Europe. A number of these are undergoing clinical trials and in future, many more molecules could be identified as potential therapeutic targets for cancer. A good example of targeted therapy is Erbitux (cetuximab). This is a first in class IgG1 monoclonal antibody (mAb), specifically targeting the epidermal growth factor receptor (EGFR). mAbs are highly specific therapeutics and have improved side effect profiles.

This apart, there is considerable scope for newer treatment options for those patients who have a higher risk of recurrence and are in advanced stages of the disease. Treatment options here have been limited in the past, and long term survival rate is poor. This particular driver will also have a high impact on the market throughout the forecast period.

Notwithstanding these growth factors, the complex and expensive European drug registration process is threatening product advancements. In Europe, drug registration works at both central (controlled by the European Commission) and national (country-wise) authorisation levels and co-existence of two authorities means that approvals can take a longer time. On a positive note though, the European Commission has issued proposals to streamline the regulatory process and introduce a US style ‘fast track’ procedure for breakthrough and urgent medicines.

“Moreover, price and reimbursement are set on a national level rather than the European level and this can further increase the time it takes a drug to reach the market,” says Mudhar. “This is why a majority of the companies favour the United States as the leading market for product introductions, with European launches occurring approximately a year later.”

Considering that combination of therapies have been used traditionally in the treatment of head and neck cancer, future strategies for companies in this market would be to continue along these lines, rather than replace surgery or radiation therapy or chemotherapy. This can be seen from many of the pipeline drugs, where most drugs are actually proving to be most effective in combination with other modalities. In the longer term, with more research, targeted therapies are likely to achieve better results when used in monotherapy.

In a pooled analysis of 13 studies, those who quit heavy drinking saw their risk of esophageal cancer and head and neck cancer return to normal after 20 years, according to Jürgen Rehm, Ph.D., of the Centre for Addiction and Mental Health and colleagues.

But the first few years after stopping saw a significant rise in development of both types of cancer, he and colleagues reported in the September issue of the International Journal of Cancer.

The researchers postulated that the increase immediately after quitting was the result of what they called the “sick quitter” effect, in which patients stop drinking because they are already suffering symptoms of cancer, although it had not yet been diagnosed.

But after five years in the case of esophageal cancer and 10 years for head and neck cancers, the risk begins to drop, Dr. Rehm and colleagues said.

“Alcohol cessation has very similar effects on risk for head and neck cancers as smoking cessation has on lung cancer. Dr. Rehm said. “It
– takes about two decades before the risk is back to the risk of those who were never drinkers or never smokers.”

The finding comes from 13 case-control studies – five in esophageal cancer and eight in head and neck cancer – that included more than 5,000 cases, the researchers said. Most of the studies involved squamous-cell carcinoma.

Compared with current drinkers, people who have never used alcohol had a risk ratio for esophageal cancer of 0.37 and for head and neck cancers of 0.46. Both risk reductions were significant at P<0.001.

For former drinkers (compared with current drinkers) the risk first rose and then fell:

– The risk ratio for esophageal cancer in the first two years after stopping was 2.5, with a 95% confidence interval from 2.23 to 2.80, which was significant at P<0.001.

– Between five and 10 years after stopping, the risk of esophageal cancer was significantly reduced (at P<0.001) with a risk ratio of 0.85 and a 95% confidence interval from 0.78 to 0.92.

– By 15 years, the risk ratio for esophageal cancer was the same as that for a person who had never used alcohol – 0.37.

– The risk for head and neck cancers remained high for the first 10 years after going on the wagon. The risk ratio for people between five and 10 years after they quit was 1.26, with a 95% confidence interval from 1.18 to 1.35, which was significant at P<0.001.

– But between 10 and 15 years later, the risk ratio was 0.67, with a 95% confidence interval from 0.63 to 0.73, which was significant at P<0.001.

The risks did not change substantially when the researchers adjusted for smoking.

Dr. Rehm and colleagues noted that the study is limited because they treated drinking as an all-or-nothing issue, and were unable to estimate dose-response effects.

They also noted the analysis is entirely based on retrospective studies, which opens the door to various errors, including recall bias.

Nonetheless, they said, the study is comprehensive and provides the most accurate available odds ratios for alcohol cessation. “The risk reductions are quite large, especially for esophageal cancer,” they said.

The study was supported by Public Works and Government Services Canada.

Introgen reports the results of new data analysis from multiple Phase 2 clinical studies showing a statistically significant correlation between the abnormal p53 biomarker and tumor response after treatment with Advexin in patients with head and neck, lung, prostate and Li-Fraumeni Syndrome cancers.

In 54 late-stage cancer patient samples evaluated from the Company’s Phase 2 studies, tumor response after Advexin monotherapy was observed in 35% of patients with the abnormal p53 biomarker and all tumor responses occurred in the abnormal p53 biomarker group (p = 0.0013). The majority of these patients had recurrent disease after receiving standard therapies.

The company has previously reported study results demonstrating a statistically significant correlation between the abnormal p53 biomarker and increased survival after Advexin therapy in head and neck cancer patients.

“The results presented today confirm and extend previous biomarker data correlating the abnormal p53 biomarker with increased tumor responses following Advexin treatment and support its use as a biomarker to predict Advexin efficacy,”
said John Nemunaitis, M.D., a principal investigator of the studies and executive director of the Mary Crowley Medical Research Center.
“Importantly, the data from multiple tumor types indicate an absolute correlation of tumor response and abnormal p53 as 100 percent of the responding tumors had the abnormal p53 biomarker.”

A cancer diagnosis affects more than just the patient. A new study from researchers at the University of Michigan Comprehensive Cancer Center finds spouses report similar physical and emotional quality of life as the patient.

The study found that what really impacted emotional distress among both patients and their spouses was whether the patient was newly diagnosed, facing a recurrence or living with advanced disease.

Researchers looked at 263 men with prostate cancer and their spouses. Participants were recruited from three large cancer centers. Both the men and their wives completed questionnaires that assessed quality of life, including physical, social, family, emotional and functional issues. Patients and spouses each reported on their own quality of life.

The researchers found little difference in quality of life between patients and spouses, but found significant differences based on the phase of their illness. Couples coping with advanced disease had significantly poorer overall quality of life.

“The spouses of advanced cancer patients are really carrying the load. Cancer is a devastating illness, and a patient’s primary resource is the partner, who often doesn’t have the information she needs to deal with these complex problems. This isn’t just a common cold – this is the person you love and care about dealing with a life-threatening illness,” says lead study author Laurel Northouse, Ph.D., R.N., co-director of the Socio-Behavioral Program at the U-M Comprehensive Cancer Center and Mary Lou Willard French Professor of Nursing at the U-M School of Nursing.

Results of the study appear in the Sept. 20 issue of the Journal of Clinical Oncology.

Spouses reported lower confidence than patients in their ability to manage the illness, and more uncertainty about the illness. Patients also reported more social support than did spouses.

“Doctors, nurses and even family and friends often focus mainly on the patient who has cancer and don’t realize the illness has enormous ramifications on the family, especially the spouse,” Northouse says.

The researchers urge more health care interventions aimed at emotional distress for both patients and caregivers. At the same time, caregivers should recognize they too are emotionally affected by this illness and seek appropriate support. Patients also can play a role by encouraging their spouse to be actively involved in their care.

“Patients need to recognize this illness affects their partners as well as themselves. They need to find a way to be supportive of their partner; for example, including them in interactions with physicians so the partners get the information they desperately want. Work as a team together to deal with the illness. I think patients may underestimate the needs of their partners to get information. Those partners need first-hand information. If they’re able to go into the consultation, they’re able to get their questions answered,” Northouse says.

Infection with human papillomavirus (HPV) is emerging as a significant factor in head and neck squamous-cell carcinoma—with medical and perhaps social implications.

“HPV-related oropharynx carcinoma is beginning to constitute a significant portion of the oncologist’s practice in head and neck cancer,” said Marshall Posner, MD, medical director, Head and Neck Oncology Program, Dana-Farber Cancer Institute, Boston, who presented new study results at the annual meeting of the American Society of Clinical Oncology (ASCO). “HPV-related cancers are seen in as many as 25% of patients in community practice. At Dana-Farber, a referral cancer center, almost 50% of the oropharynx cancers we see are HPV-positive.”

HPV Infection Improves Prognosis

But the presence of HPV infection actually heralds a better prognosis in patients with these types of cancer, according to data from a new phase 2 prospective study conducted by the Eastern Cooperative Oncology Group (ECOG 2399).

This multicenter study confirmed retrospective, single-institution reports showing improved survival for patients with HPV-positive head and neck squamous-cell cancer compared with their HPV-negative counterparts. At ASCO, Carole Fakhry, MD, of the Johns Hopkins Medical Institutions, Baltimore, reported that a positive HPV infection status conferred a 79% lower risk of death in this population.

HPV status should now be considered a biomarker for prognosis in head and neck cancer, Dr Fakhry maintained. Moreover, these findings have implications for current treatment practices, as they may necessitate a reinterpretation of survival rates found in previous phase 2 trials to determine whether survival was the result of therapeutics or, in fact, the result of HPV status, she said.

New Study Results

The ECOG 2399 trial assessed organ preservation, disease-free survival; and patterns of failure with taxane-based induction chemotherapy followed by taxane-based concurrent chemoradiation in 96 patients with resectable stage III and IV larynx and oropharyngeal cancer. Investigators related the presence of HPV infection with prognostic factors, treatment response, and survival outcomes. They were particularly interested in HPV-16, the dominant viral isolate known to be responsible for a subset of head and neck cancers, along with HPV types 31, 33, and 35, the other isolates linked to these tumors.

HPV-positive tumors were detected in 40% of the patients; all cancers were oropharyngeal (Figure). Compared with HPV-negative patients, HPV-positive patients were more likely to:

– Have a better performance status
– Have a lower lifetime exposure to smoking
– Have less weight loss on presentation
– Be male
– Present with earlier-stage primary/ more-advanced nodal-stage tumors.

Of note, the patients who were HPV-positive had significantly higher response rates to induction and to chemoradiation therapy.

After more than 3 years of follow-up, the risk of disease progression was 72% lower, and the risk of death was 79% lower, in the HPV-positive patients as compared with the HPV-negative patients, Dr Fakhry said.

A Changing Epidemiology

Anil K. Chaturvedi, PhD, of the National Cancer Institute, Rockville, reported results of another study, which also investigated the relationship between HPV infection and head and neck squamous-cell carcinoma. Dr Chaturvedi said that HPV-related head and neck cancer has increased over the past 30 years, particularly among white men aged 40 to 59 years.

Using data from the Surveillance, Epidemiology, and End Results (SEER) registry for the period from 1973 to 2003, Dr Chaturvedi found that HPV-related tumors were being diagnosed at more advanced stages, and at a significantly younger age. The incidence of HPV-unrelated cancers, on the other hand, decreased in both men and women, especially in those over the age of 40. These trends became noticeable in the early 1990s.

Dr Chaturvedi proposes that the increasing incidence of HPV-associated tumors could be caused by changes in sexual behavior, and that the decreasing incidence of HPV-unrelated cancers could be the result of the decreasing prevalence of smoking.

In contrast to the once-traditional profile of the patient with head and neck cancer, up to 25% of the patients with this type of cancer are now:

– HPV-positive
– Young
– Nonsmoking
– Nondrinking.

Thus, today’s patients are often not diagnosed in a timely manner. But as evidence from the ECOG study shows, the life expectancy of the HPV-positive patients is actually higher, probably because they are, in general, healthier individuals, suggests Dr Posner.

Clinical Implications

“I believe this ‘epidemic’ of HPV disease is going to change the demographic and the urgency of treatment in this cancer,” Dr Posner maintains. “The fact that HPV-positive tumors have a better prognosis than oropharynx cancer caused by smoking is extremely important, because curing these patients will mean dealing with long-term sequelae in a young population living longer after treatment—living with scarring and fibrosis, as well as other complications from radiation, including a risk for second cancers,” he says.

He adds that in spite of the better prognosis for HPV-related tumors, aggressive treatment is critical. “We must remember that the improved prognosis for HPV-16 in the ECOG study was after a very intensive sequential therapy regimen that included aggressive induction chemotherapy and chemoradiotherapy. This does not mean we can lower the intensity of treatment for these patients and expect to maintain high cure rates. In our own practice, we have seen HPV-positive distant metastases in HPV-positive oropharynx patients treated with chemoradiotherapy alone.”

The prevalence of HPV-related oropharynx cancer also raises other issues, Dr Posner notes. “One, because this is a sexually transmitted disease, in which sexual practices [oral sex] increase risk, we must ask whether the patient’s significant other or sexual partners should be vaccinated or tested. Do they need surveillance? And what about children? It is possible that HPV is transmitted by saliva,” he asks. “These are questions for which we do not yet have the answers.”

KEY POINTS
– HPV-associated cancers are now seen in about 25% of patients in community practice and in almost 50% at cancer centers.
– Unlike the characteristics of the traditional patient, about 25% of current patients with head and neck cancer are HPV-positive, young, nonsmoking, and nondrinking.
– In a new study, a positive HPV infection status conferred a 72% lower risk of disease progression and a 79% lower risk of death.

A U.S. pathologist says some anti-cancer treatments may shrink tumors but increase the cancer stem cells that drive the disease.

Dr. Vasyl Vasko of the Uniformed Services University of the Health Sciences said his research suggests that some treatments could be producing more cancer stem cells, which then metastasize as a way to survive the therapy.

“This may help explain why the expression of stem-cell markers has been associated with resistance to chemotherapy and radiation treatments and poor outcome for patients with cancers including prostate, breast and lung cancers,” Vasko said Friday in a release.

The research was presented at the American Association for Cancer Research’s second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

The report said the cancer stem-cell markers include Nanog and BMI1, both of which contribute to stem cells’ defining ability to renew themselves and differentiate into different cell types. Vasko said these same molecules are found in embryonic stem cells.

The Health Protection Agency’s study confirms that a significant proportion of young women are having sex between the ages of 14 and 16. The finding of positive antibodies to HPV, the human papillomavirus, which can infect anyone, man or woman, who has sexual intercourse, is a good marker for sexual activity.

Although 80 per cent of women become HPV positive during their lives, in only a small minority of cases does it give rise to either premalignant or malignant changes in the cervix. Most people are unaware when they are infected with HPV because the obvious genital wart is not of the type that turns malignant. It takes between ten and twenty years for cervical cancer to develop after infection.

Well over 99 per cent of cases of cervical cancer can be shown to have been caused by infection with HPV. Different strains of HPV from those that cause cervical cancer result in the unsightly and troublesome genital warts. HPV is also certainly responsible for many cases of anal and penile cancer and it is thought by many doctors to account for the marked upsurge in cases of oral cancer over the past 30 years that has coincided with an increase in oral sex.

It has been known for many years that far more young girls, from all walks of life, are having sex when still under age than their mentors liked to assume. For this reason it is important that girls especially, but preferably both boys and girls, should be vaccinated against HPV before they are likely to start sexual intercourse. If boys are not vaccinated they will remain a pool of infection and the vaccination will not prevent the other cancers related to HPV. The vaccination currently available will give only 80 per cent protection because it does not cover all the five sub-types of virus that are known to cause malignancies.